The present invention relates to a method of sorting and possibly also of concentrating submillimetric particles or submillimetric particle clusters in a fluid flowing in a main channel.
Methods are already known for passive hydrodynamic sorting downstream from a periodic array of obstacles that, in each row of studs, deflects all particles larger than a critical size in the same direction, which size that is determined by the geometry of the device. With the path of the larger particles thus being inclined relative to the path of the smaller particles, it is possible to separate cells as a function of their size.
Such a technique is described in particular in the following applications: WO 2004/037374 (Huang); US 2007-026381 (Huang); or indeed US 2007-059782 (Kapur).
Another passive sorting method implements two laminar flows, namely a buffer containing particles and a particle-free focusing buffer, which buffers are urged into a narrow channel prior to penetrating into a wider channel. In that method, focusing enables the particles to be positioned against the opposite wall of the channel. The focusing is performed by laterally injecting a particle-free fluid and it is encouraged by the geometrical constriction. It enables the positions of the particles relative to the wall to be made different as a function of particle size, with the enlargement of the section enabling sorting to be performed. Thus, the smallest particles have their centers of inertia at a distance x1 (very small) close to the wall of the channel on which focusing is performed, while larger particles have their centers of inertia at a distance x2 that is greater than x1.
On passing from the pinch region to the region of enlarged section, the position difference between flow lines is emphasized, and since the particles follow the flow lines on which their centers of inertia are located, enlarging the channel emphasizes the differences in position between small and large particles.
The pinching of the flow presents the drawback of exerting shear stresses on the particles when they reach the narrow channel, and above all, because of its geometry, it gives rise to the particle samples being diluted, and the technique used does not provide any remedy for that. Such a technique is described in particular in the document “Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel” by Masumi Yamada et al. (Analytical Chemistry, Vol. 78, No. 18, Sep. 15, 2004, pp. 5465 to 5471).
Another known technique is an active sorting method whereby the flow lines of a fluid containing particles are deflected by locally creating a low pressure zone by suction. The paths of the particles depend on the overall balance of forces applied to the particles: as a function of their weights, densities, volumes (or diameters), and speeds, and as a function of the pressure field that results from the suction, particles are either sorted or not. Such a technique is proposed in US application No. 2007/221550 (WO 2006/102258) in the name of Barton Smith and Zachary Humes.
Yet another known technique is hydrodynamic filtering, which is described in particular in the article by Masumi Yamada and Minori Seki entitled “Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics”, The Royal Society of Chemistry, 2005, Lab Chip 2005, 5, pp. 1233 to 1239. That method implements low rate flows in lateral channels firstly for concentrating and aligning the particles, and secondly for selecting them. Particle concentration along the walls requires a large number of lateral channels of low flow rate and of very accurate geometrical dimensions.
It is also known to make use of microvortices to trap small fluorescent particles (with size of micrometer order). That technique is described by D. Lim et al. in “Dynamic formation of ring-shape patterns of colloidal particles in microfluidic systems”, Applied Physics Letters 2003, 83 (6), pp. 1145 to 1147. That method requires high-speed ranges.
A method of separating particles according to their density by centrifugal recirculation is described by Shelby et al. in “High radial acceleration in microvortices” published in Nature 2003, 425, pp. 38 et seq., for separating two types of bead having different densities (polystyrene beads with a density of 1.05 grams per cubic centimeter (g/cm3) and silica beads of density in the range 1.8 g/cm3 to 2 g/cm3). Centrifugal recirculation serves to concentrate the low density beads in the center of the vortex and the higher density beads towards the walls of the chamber. That method requires high speeds (of the order of 20 meters per second (m/s)), together with a large difference in density between the particles. Finally, it does not enable the separated particles to be recovered.
That method therefore does not serve to sort or concentrate particles, but rather to separate particles by applying high centrifugal force (centrifugal acceleration of the order of 104 meters per second per second (m/s2)) with high levels of shear (of the order of 105 pascals (Pa)) in the recirculation zones.